J. Lauwereyns, Ph.D. Professor Graduate School of Systems Life Sciences Kyushu University Basic neuroscience Impulses and synapses

The axon and its terminal

Following an action potential: Neurotransmitters will be released in the synaptic cleft and influence the post-synaptic neuron… Need to get through the membrane

The membrane Double layer of lipid molecules Heads Tails Heads

The Semi Permeable Plasma Membrane Double layer of lipid molecules (phospholipids) Outside of axon Inside of axon Heads Tails Heads Water ‘loving’ (hydrophilic) Water ‘fearing’ (hydrophobic)

Ionic concentrations Na + (Sodium) (10) Outside of axon Inside of axon Cl - (Chloride) (11.5) K + (potassium) (20) A - (Anions -impermeable negatively charged proteins ) K + (1) Na + (1) Cl - (1)

The movement of ions Diffusion (concentration gradient) Electrical (electrostatic gradient) Sodium / Potassium pump

Diffusion (concentration gradient )

Electrical (electrostatic gradient) Opposite charges attract Like charges repel

Resting potential The membrane’s resting potential is –70 mV (conventionally measured inside the cell)

An experiment

Applying a small depolarizing stimulus is not enough to trigger an action potential

Turning up the volume of stimulation still is not enough to reach the threshold for activation

Here we go, with a stimulus that depolarizes the membrane to about -60 mV…

Now, suppose we can program the stimulator so that it gives a hyperpolarizing stimulus… No action potential -

-+ And if we first present a hyperpolarizing stimulus, followed shortly by a depolarizing stimulus ( which normally would be strong enough )… No action potential

Back to the membrane… Inside the cell Outside the cell A-A- K+K+ K+K+ Cl - Na + Potassium Chloride Sodium Organic anions

The membrane’s permeability How easily can particles move from inside to outside? A - cannot pass (impermeable) K + passes easily (high permeability) Na + does not pass easily (low permeability)

Diffusion vs. electrostatic pressure Outside the cell A-A- K+K+ K+K+ Cl - Na + Potassium Chloride Sodium Organic anions How come there is so much Na + outside? The trick is the Sodium-Potassium pump, pushing three sodium ions out for every two potassium ions it pushes in…

Sodium-potassium (Na + /K + ) pump Membrane-spanning protein Pumps 2K+ into cell and 3Na+ out. This pump requires energy (ATP) Why is energy needed? ……..ions moved against electrostatic and concentration gradients

In short Balance between forces Sodium-Potassium pump What if the membrane suddenly became more permeable to, say, sodium?

Action potential Is the disturbance of the membrane’s resting potential Sudden reversal of potential For a fraction of a millisecond, the inside of the axon becomes positive, relative to the outside. Then the resting potential is restored

Threshold Overshoot Undershoot Rising phase Falling phase

How does an action potential work? Look at what happens with ion channels… Both types of channels are voltage-dependent; That is, they open depending on whether the membrane is depolarized to a particular value

Once an action potential gets triggered, sodium channels open first

Sodium flows in, and so the membrane depolarizes further

Then the potassium channels open, however, there is still little electrostatic pressure for potassium to flow out

At the peak of the action potential the sodium channels become refractory: sodium can’t pass, potassium flows out in bulk and turns the tide

After having caused the membrane to become negative again, the potassium channels begin to close

Finally, the sodium channels begin to close, and the membrane goes back to its resting potential

The neuron

An action potential starts here, at the “axon hillock”

The neuron And then moves from the “axon hillock”, down the axon, to the terminals

Why does the action potential move in one direction?

Refractory period Primarily due to the temporary blocking of voltage gated sodium channel.

Saltatory conduction from the Latin ‘saltare’, to hop or dance The initiation of an action potential in one node of Ranvier depolarises the next node. Jumping from one node to the next

The origin of an action potential At the axon hillock Leads to an action potential in the post-synaptic neuron Excitatory A/P